CTLA-4 单核苷酸多态性在接受 CAR-T 细胞治疗的弥漫大 B 细胞淋巴瘤患者中的临床影响

FMC63-CAR T cell therapy targeting CD19 protein on malignant B-cells is effective in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL), with complete response rates of 43-54%. Common germline variants of the immune-checkpoint regulator CTLA-4 may elicit different responses to CAR-T cell therapy. The CTLA4 gene single-nucleotide polymorphism rs231775 coding threonine or alanine at amino acid position 17 of the CTLA-4 protein was prevalent in 55% of the studied DLBCL patients.

In a retrospective comparative analysis of clinical outcome, there were significant differences in CTLA4 A17hom vs. T17Ahet and T17hom carriers with four-year progression-free survival at 77%, 59%, and 30% ( p = 0. 019), four-year overall survival was 79%, 41%, and 33% ( p = 0.

049), the relapse rates were 20%, 37%, and 56% ( p = 0. 025), and the death rates 20%, 54%, and 52% ( p = 0. 049). Conclusions: CTLA4 rs231775 polymorphism may impact the treatment outcome in FMC63-anti-CD19 CAR-T cell therapy, with an association of the CTLA4 minor allele A17 to favorable treatment outcome.